The glucocorticoids and glucagon interact to regulate gluconeogenesis in liver. The role of the glucocorticoids has been termed permissiive since these hormones by themselves produce only a slight stimulation of gluconeogenesis but are required for full expression of the glucagon effects. The objective of the proposed research is to investigate the mechanism by which the glucocorticoids maintain the normal responsiveness of hepatocytes to hormones which act through cyclic AMP. Adult rat liver parenchymal cells in primary culture will be used. Hormonal modulation of glucose production and amino acid transport will be correlated with changes in the cellular phosphoprotein profile. The subcellular location of the phosphoproteins of interest will be determined. This study should provide useful information for further understanding the contribution of the liver to glucose homeostasis.